Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Kidney Int. 2021 Jul;100(1):196-205. doi: 10.1016/j.kint.2020.12.015. Epub 2020 Dec 24.
Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
免疫检查点抑制剂（ICI）广泛用于各种恶性肿瘤。然而，它们在肾移植患者中的安全性和疗效尚未确定。为了阐明这一点，我们对 2010 年 1 月至 2020 年 5 月期间接受 ICI 治疗的 69 例肾移植患者进行了一项多中心回顾性研究。为了评估安全性，我们评估了急性移植物排斥反应的发生率、时间和危险因素。为了评估疗效，我们评估了皮肤鳞状细胞癌和黑色素瘤患者的客观缓解率和总生存率，这是我们队列中最常见的癌症，并与接受 ICI 治疗的 23 例皮肤鳞状细胞癌和 14 例黑色素瘤患者进行了比较，这些患者没有接受 ICI 治疗。在接受 ICI 治疗后，69 例患者中有 29 例（42%）发生急性排斥反应，其中 19 例失去了移植物，而非 ICI 组的急性排斥反应发生率为 5.4%。从 ICI 开始到排斥反应的中位时间为 24 天。与较低排斥反应风险相关的因素包括 mTOR 抑制剂的使用（比值比 0.26；95%置信区间，0.09-0.72）和三联免疫抑制（0.67，0.48-0.92）。在鳞状细胞癌和黑色素瘤亚组中，客观缓解率分别为 36.4%和 40%。在鳞状细胞癌亚组中，接受 ICI 治疗的患者总生存率显著延长（中位总生存率 19.8 个月与 10.6 个月），而在黑色素瘤亚组中，两组之间的总生存率没有差异。因此，ICI 在肾移植患者中与较高的排斥反应风险相关，但可能导致癌症结局改善。需要前瞻性研究来确定最佳的免疫抑制策略，以改善患者的预后。
